The Rx Factor

FDA takes action on prescription pain relievers

By Sarah Aldridge | 07.25.2011

Originally Published July 2011

Because many pain relievers (including aspirin-containing products) can cause internal bleeding, acetaminophen is generally considered a safe alternative for people with bleeding disorders. However, too much of it can cause complications. The Food and Drug Administration (FDA) is protecting the public by taking steps to prevent harmful side effects from acetaminophen and propoxyphene in prescription pain medications.

Acetaminophen

In January 2011, the FDA requested that all manufacturers of prescription products containing acetaminophen limit the amount to 325 mg or less. Current products contain up to 750 mg per capsule or tablet. The action was taken to prevent liver damage, which can occur when patients take more than one product containing acetaminophen; drink alcohol while on it; or exceed the recommended daily dose for adults of 4,000 mg/day.

Patients on prescription pain medicine may not realize acetaminophen is found in the popular opioid pain relievers hydrocodone (Vicodin) and oxycodone (Percocet). It is also an ingredient in many cough and cold medications.

Acetaminophen itself is not the culprit in causing liver injury. The byproducts that result when it is metabolized do the harm. Exceeding the maximum daily amount inhibits the liver’s ability to metabolize the drug. Toxic byproducts then build up, which inflame the liver and damage its cells. Acetaminophen is usually not recommended for patients with HIV, because it can suppress the immune system, or who have hepatitis C, because the liver is already compromised.

“It’s not that acetaminophen is a bad drug,” Witkop says. “For the bleeding disorders population, it can be used. But you have to look at how much you are taking in combination with other medications.” Further, you cannot take acetaminophen and continue to drink alcohol, which accelerates liver damage, she stresses. This is even more important for patients with other co-morbidities, such as hepatitis C, says Witkop.

According to the American Association for the Study of Liver Diseases, acetaminophen overdoses cause 50,000 emergency room visits and 500 deaths annually in the US. “Overdose from prescription products containing acetaminophen account for nearly half of all cases of acetaminophen-related liver failure in the US, many of which result in liver transplant or death,” says ­Sandra Kweder, MD, deputy director of the FDA’s Office of New Drugs.

Now prescription products containing acetaminophen must contain the FDA’s so-called “black box warning” label, its strongest alert. The label will state that liver damage can result from acetaminophen overdose. Over-the-counter products with acetaminophen already bear the black box warning label.

Propoxyphene

Darvon, a popular prescription drug containing propoxyphene, was used for more than 50 years to alleviate mild to moderate pain. Now it is on its way out. So is Darvocet, which contains propoxyphene and acetaminophen. Both can produce severe heart rhythm disturbances. Xanodyne Pharmaceuticals Inc., the main manufacturer, agreed to voluntarily withdraw the drugs after a request from the FDA in November 2010.

For years, Darvon’s side effects have been weighed against its benefits. In Britain, the drug was withdrawn in 2006 due to heightened risk of suicide and accidental overdose. In 2009, the FDA required a black box warning on the label about the potential for fatal overdose. In 2010, a study conducted by Xanodyne indicated that propoxyphene increased the risk for heart rhythm abnormalities that could lead to death, even in patients taking the recommended amount.

“The data suggested that the heart risk of propoxyphene could apply to all users, and not just those who took excessive doses or those with medical conditions that might reduce their ability to clear propoxyphene from the body, such as patients with reduced kidney function,” says John Jenkins, MD, director of the FDA’s Center for Drug Evaluation and Research.

The study indicated the potential for cardiac arrest, or sudden heart death, from serious abnormal heart rhythms. In addition, the data showed that minor changes in a patient’s health, such as dehydration or decreased kidney function, could increase the risk of adverse effects from propoxyphene. Patients who are on Darvon or Darvocet should consult their physician before they stop taking the medication.

Pain Relief Alternatives

Talk to your provider about pain relief alternatives that will work for you. Rarely is there a single medication that will relieve all of your pain, though.

“We take a multimodal approach to pain management, hitting it from different mechanisms, pharmacologically and nonpharmacologically,” Witkop says. Opioids help relieve some types of pain, while neuropathic drugs help when nerves become irritated after a joint bleed, she says.

Witkop is also a proponent of nondrug alternatives. Ice, compression and elevation can help; so can distraction techniques, she says. “Guided imagery, hypnosis and biofeedback are other alternative methods of pain management.” The key is finding the right combination that works for you.